Significant progress has been made in identifying genes and molecular pathways that may be involved in Alzheimer disease pathogenesis. Unfortunately, we still have a limited understanding of how these genes and pathways ultimately trigger Alzheimer disease symptoms and disease progression. Animal models of Alzheimer disease have failed to recapitulate the spectrum of neuropathological changes observed in the human Alzheimer disease brain and despite advances in the clinical recognition of Alzheimer's disease, definitive diagnosis requires careful examination of autopsy brain tissue. Research utilizing properly collected and preserved brain tissue and other biologic samples from Alzheimer disease patients, non-Alzheimer dementia patients and normal aged controls is essential for advancing our knowledge of the cellular and molecular mechanisms responsible for the development of Alzheimer disease. The long-term goal of the UAB Neuropathology Core Laboratory is to support research which furthers our understanding of the molecular mechanisms of Alzheimer disease, improves the daily life of patients with Alzheimer disease and points to new therapeutic approaches. To achieve these goals, the UAB Neuropathology Laboratory proposes to: 1) Accurately diagnose the neuropathologic abnormalities in Alzheimer patients and those with other dementing illnesses using the NIA-Reagan Institute Working Group criteria and modern neuropathological techniques; 2) Rapidly collect and properly preserve precisely dissected brain tissues and other biological specimens from autopsied Alzheimer disease cases, non-Alzheimer dementia patients and cognitively normal aged controls; and 3) Properly maintain our extensive collection of precisely dissected and preserved brain tissues and other biological specimens from Alzheimer disease cases, non-Alzheimer dementia cases and cognitively normal aged controls and to provide specimens from this collection to intramural and extramural investigators studying Alzheimer disease. By working to provide services necessary to support the other components of the UAB Alzheimer Disease Research Center and facilitating Alzheimer disease research by other investigators, both inside and outside the UAB research community, we will significantly expand the ability of these collaborating investigators to conduct both basic and clinical research into Alzheimer disease